A proof-of-concept study to investigate the radiolabelling of human mesenchymal and hematopoietic stem cells with [(89)Zr]Zr-Df-Bz-NCS

一项概念验证研究,旨在探讨使用[(89)Zr]Zr-Df-Bz-NCS对人类间充质干细胞和造血干细胞进行放射性标记的方法。

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Abstract

BACKGROUND: The transplantation of hematopoietic stem and progenitor cells (HSPCs) or mesenchymal stromal/stem cells (MSCs) for the treatment of a wide variety of diseases has been studied extensively. A challenge with cell-based therapies is that migration to and retention at the target site is often difficult to monitor and quantify. Zirconium-89 ((89)Zr) is a positron-emitting radionuclide with a half-life of 3.3 days, which allows long-term cell tracking. Para-isothiocyanatobenzyl-desferrioxamine B (Df-Bz-NCS) is the chelating agent of choice for (89)Zr-cell surface labelling. We utilised a shortened labelling method, thereby avoiding a 30-60-min incubation step for [(89)Zr]Zr-Df-Bz-NCS chelation, to radiolabel HSPCs and MSCs with zirconium-89. RESULTS: Three (89)Zr-MSC labelling attempts were performed. High labelling efficiencies (81.30 and 87.30%) and relatively good labelling yields (59.59 and 67.00%) were achieved with the use of a relatively larger number of MSCs (4.425 and 3.855 million, respectively). There was no significant decrease in MSC viability after (89)Zr-labeling (p = 0.31). This labelling method was also translatable to prepare (89)Zr-HSPC; preliminary data from one preparation indicated high (89)Zr-HSPC labelling efficiency (88.20%) and labelling yield (71.06%), as well as good HSPC viability after labelling (68.65%). CONCLUSIONS: Successful (89)Zr-MSC and (89)Zr-HSPC labelling was achieved, which underlines the prospects for in vivo cell tracking studies with positron emission tomography. In vitro investigations with larger sample sizes and preclinical studies are recommended.

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